ADENOASSOCIATED VIRUS VECTORS FOR GENE-THERAPY

Adeno-associated virus type 2 (AAV) is a non-pathogenic DNA virus whic h has been utilized as a eukaryotic gene transfer vector in vitro and in vivo. AAV possesses a unique set of characteristics which may make it useful for human gene therapy. AAV infection does not require host cell proliferation, although expression from AAV vectors may exhibit a relative preference for actively dividing cells. Both wild-type AAV a nd AAV vectors tend to persist in infected cells for prolonged periods of time, without any significant adverse consequences for the host. W ild-type AAV integrates frequently in one specific region of chomosome 19 whereas rep-deleted AAV vectors integrate in a less specific fashi on in the host cell genome and may also persist in an episomal state. AAV vectors have been used to transduce a wide range of cell types in vitro including respiratory epithelial cells as well as bone marrow an d lymphocyte-derived cells. As a prelude to AAV-based gene therapy for cystic fibrosis (CF), in vivo transduction and expression in the lung s has been observed in rodents and non-human primates after direct del ivery to the airway surface, without any detectable toxicity. Based on these findings, the National Institutes of Health Recombinant DNA Adv isory Committee (RAC) has recently approved a phase I human trial of C F gene therapy using an AAV vector.